Glucose Metabolic Reprogramming in Colorectal Cancer: From Mechanisms to Targeted Therapy Approaches

ABSTRACT Background Colorectal cancer (CRC) is one of the most common malignant tumors, and its morbidity ranks third among all cancers, with a trend toward younger patients. Metabolic reprogramming, a unique metabolic mode in tumor cells, is closely related to the occurrence and development of CRC. Numerous studies have confirmed that many genetic and protein changes can regulate cellular metabolic reprogramming, of which changes in glucose metabolism have the greatest impact. These aberrant metabolic processes provide energy and essential nutrients to CRC cells, promoting their proliferation and metastasis and influencing tumor resistance. The purpose of this review is to outline the role of glucose metabolic reprogramming in the onset and development of CRC, discuss the research progress in the dual reprogramming of glucose metabolism and lipid metabolism or glucose metabolism and amino acid metabolism, and address the issues of targeted metabolism therapy and drug resistance. Methods We searched PubMed for review articles published in English between January 1, 2015, and April 26, 2024, which included “Colorectal Neoplasms” with “Metabolic Reprogramming” OR “Glucose Metabolism Disorders” OR “The Warburg Effect” OR “Targeted Therapy.” Subsequently, the literature was classified, organized, and summarized. Various types of studies were integrated and compiled into this review. Additionally, mechanism diagrams were drawn to facilitate the understanding of this study. The figures were created using BioRender.com and has obtained the official publication license. Conclusions Glucose metabolic reprogramming serves as a pivotal driver of CRC initiation, progression, and chemoresistance, while its crosstalk with lipid or amino acid metabolic reprogramming further amplifies the malignant phenotype of CRC. Targeted therapeutic strategies aiming at glucose metabolic reprogramming (such as metabolic inhibitors, combination with immunotherapy) and related clinical research have demonstrated potential for inhibiting CRC progression and improving treatment outcomes.